It is desirable to identify compounds that sufficiently cleanse the colon, but do not cause adverse side effects. It is also desirable to identify compounds that are used to treat constipation and promote fecal elimination, for instance, but that do not produce uncomfortable or embarrassing side effects such as gas. Additionally, completely clearing the bowel of fecal debris is a necessary prerequisite before a variety of diagnostic and surgical procedures. Cleansing is important, for instance, in order to sufficiently view the gross or microscopic appearance of the colon during colonoscopy. However, the cleansing procedure must also be tolerable to patients so that they are fully compliant with the cleansing process. Poor bowel preparation, due to lack of patient compliance or insufficient cleansing, impacts the efficiency and cost of these procedures, especially if they must be repeated (Rex et al. (2002) Am. J. Gastroenterol. 97:1696-1700). Further, patients may not elect to undergo uncomfortable diagnostic procedures, which would significantly reduce early detection of disorders and increase medical costs. (Harewood et al. (2002) Am. J. Gastroenterol. 97:3186-3194).
Colonic cleansing is commonly accomplished using lavage with polyethylene glycol-electrolyte solutions. A major disadvantage of this method is that patients are required to ingest a significant amount of liquid volume within a short period of time for purgation. For instance, patients may have to ingest four liters of solution within a period of two to three hours (Afridi et al. (1995) Gastrointest. Endosc. 41:485-489). A large number of patients experience significant volume-related discomfort and adverse side effects such as nausea, cramping, and vomiting (Dipalma et al. (2003) Am. J. Gastroenterol. 98:2187-2191). Another drawback of these preparations is their salty taste, which may also lead to patient noncompliance and adverse effects. Attempts have been made to make the taste more palatable, for instance by flavoring or reducing salt content. However, these changes did not make the regimen more acceptable to the patient, nor was there an improvement in the quality of colon cleansing (Church (1998) Dis. Colon Rectum 41:1223-1225). Such preparations deter patients from colon cancer screening (Harewood et al. (2002) Am. J. Gastroenterol. 97:3186-3194).
In an attempt to avoid the problems associated with the high-volume type preparations, smaller-volume aqueous preparations consisting of phosphate salts have been marketed. The phosphate salt solution produces an osmotic effect, causing large amounts of water to be drawn into the bowel, thereby promoting bowel evacuation. Although the lower volume marginally favors these sodium phosphate preparations, adverse side effects such as nausea, vomiting (principally a result of unpalatable taste), abdominal bloating, pain and dizziness were of similar frequency compared to polyethylene glycol-electrolyte lavage (Kolts et al. (1993) Am. J. Gastroenterol. 88:1218-1223).
Oral tablets containing phosphate salts have been formulated (see U.S. Pat. Nos. 5,616,346 and 6,162,464) to increase preparatory compliance, reduce volume discomfort, and increase patient tolerance. The oral tablet formulation significantly reduced the incidence of gastrointestinal adverse events such as nausea, vomiting, and bloating (Rex et al. (2002) Aliment Pharmacol. Ther. 16:937-944). Further, these tablet formulations were significantly better accepted and preferred by patients. Applicants discovered, however, that these formulations were limited in their acceptance by physicians by the presence of visible microcrystalline cellulose (MCC) in the colon, especially in the cecum and ascending colon (FIG. 1). MCC, a purified form of cellulose, is used as a binder in the tablet formulation and is not soluble in the alimentary fluid. Retained MCC can be removed by suctioning or irrigation, so that the colon can be adequately visualized. However, these processes may prolong colonoscopy procedure time (Rex et al. (2002) Aliment Pharmacol. Ther. 16:937-944; Balaban et al. (2003) Am. J. Gastroenterol. 98:827-832), thereby prolonging the time that the patient is under anesthesia and reducing productivity of physicians (Rex et al. (2002) Am. J. Gastroenterol. 97:1696-1700). These tablets, however, were also large and difficult for some to swallow.
Thus, there is need for colonic purgative compositions that can be tolerated by the patient, while also providing quality preparation of the bowel. Further, it is desirable that the composition provides adequate visualization of the colon and structures, without the need for additional removal steps.
It is also desirable to identify a preparation that could be produced easily and used either as a complete purgative or as a laxative for mild catharsis, depending on the dosage administered. Such a dual function composition would be very beneficial.